Transformation of nonfunctional spinal circuits into functional states after the loss of brain input


After complete spinal cord transections that removed all supraspinal inputs in adult rats, combinations of serotonergic agonists and epidural electrical stimulation were able to acutely transform spinal networks from nonfunctional to highly functional and adaptive states as early as 1 week after injury. Using kinematics, physiological and anatomical analyses, we found that these interventions could recruit specific populations of spinal circuits, refine their control via sensory input and functionally remodel these locomotor pathways when combined with training. The emergence of these new functional states enabled full weight-bearing treadmill locomotion in paralyzed rats that was almost indistinguishable from voluntary stepping. We propose that, in the absence of supraspinal input, spinal locomotion can emerge from a combination of central pattern-generating capability and the ability of these spinal circuits to use sensory afferent input to control stepping. These findings provide a strategy by which individuals with spinal cord injuries could regain substantial levels of motor control.

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Figure 1: Accessing spinal locomotor circuits 1 week after the interruption of all supraspinal input.
Figure 2: Kinematics and EMG features of locomotor patterns.
Figure 3: Site-specific effects of EES during standing and stepping.
Figure 4: Rehabilitation locomotor training enabled by pharmacological and EES interventions improves stepping ability.
Figure 5: Functional remodeling of spinal circuits after rehabilitative locomotor training.
Figure 6: Effects of velocity-dependent afferent input on motor patterns.
Figure 7: Effects of load-dependent afferent input on motor patterns.
Figure 8: Effects of direction-dependent afferent input on motor patterns.


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We would like to acknowledge the excellent technical help provided by S. Zdunowski, L. Friedli, J. Heutschi and O. Märzendorfer for data collection and analysis, as well as M. Herrera for his expert assistance and guidance involving the care and handling of the animals. This work was supported by the Craig H. Nielsen Foundation (#20062668), the International Paraplegic Foundation (P106), the National Center of Competence in Research 'Neural Plasticity and Repair' of the Swiss National Science Foundation, the Christopher and Dana Reeve Foundation (VEC-2007), the US National Institute of Neurological Disorders and Stroke (NS16333), the US Civilian Research and Development Foundation (RUB1-2872-07), the Roman Reed Spinal Cord Injury Research Fund of California and the Russian Foundation for Basic Research (07-04-00526 and 08-04-00688).

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G.C., Y.P.G., I.L., M.V.S. and V.R.E. designed the study. G.C., R.R.R., H.Z. and P.M. performed the surgeries. G.C., Y.P.G., R.v.d.B., P.M. and A.Y. carried out the experiments. G.C., A.Y., B.S., Y.A., R.I. and M.V.S. conducted the anatomical assessments. G.C. analyzed the data. G.C., R.R.R., M.V.S. and V.R.E. wrote the manuscript. G.C. supervised the study.

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Correspondence to Grégoire Courtine.

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Accessing spinal locomotor circuits. (MOV 3260 kb)

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Accessing spinal locomotor circuits. (MOV 3260 kb)

Learning in spinal locomotor circuits. (MOV 8196 kb)

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Learning in spinal locomotor circuits. (MOV 8196 kb)

Control of spinal locomotor circuits. (MOV 3654 kb)

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Control of spinal locomotor circuits. (MOV 3654 kb)

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Courtine, G., Gerasimenko, Y., van den Brand, R. et al. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci 12, 1333–1342 (2009).

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